[Role of some psycho-physiological factors on driving safety]. / Ruolo di alcuni fattori psico-fisiologici sulla sicurezza alla guida.

Within a research project on the role played by human factors on road accidents, the aim of the present study is to evaluate, in young adults, the relationships between driver behaviour and personality factors as well as to assess the neuroendocrine correlates of psychological and behavioural factors investigated. Another aim is to estimate in what measure the performance levels are affected by demographic, psychological and chronobiological variables. It has been found a positive relation between highway code violations, extroversion trait of personality and Sensation Seeking scores, so confirming that this component of personality can affect risky behaviour. Furthermore the subjects more oriented to morningness chronotype were found to be prone to adopt safe driving behaviour. Regarding the relations of the neuroendocrine parameters and driving behaviour a positive correlation was observed between dopamine levels and frequency of driving violations while a negative relationship was found between adrenaline levels and frequency of driving errors. In conclusion the identification of psycho-physiological variables related to driving risky behaviour might be a useful instrument to design traffic safety programs tailored to high risk subjects.

[Monitoring occupational exposure to volatile anaesthetics in the operating theatre: environmental and biological measurements]. / Monitoraggio dell'esposizione professionale ad anestetici volatili in sala operatoria: misurazioni ambientali e biologiche.

Concentrations of nitrous oxide (N2O) and isoflurane were measured in environmental and urinary samples from subjects occupationally exposed to volatile anaesthetics in operating theatres in a hospital in northern Italy. The aim was to establish whether: an automatic analyzer (Brüel & Kjaer 1302 spectrometer) can be used for fixed position sampling ("anaesthetist zone" and "surgeon/instrument nurse zone"); periodic monitoring of anaesthetics will reduce exposure; exposure to N2O and isoflurane is within legal limits; exposure differs between anaesthetists and surgeons/instrument nurses. Exposure to anaesthetics was monitored twice at six-month intervals. In the first test time spent in the operating theatre was noted and exposure levels were measured automatically. In the second test levels were monitored with passive personal sampling devices. Environmental concentrations of N2O determined by the spectrometer were correlated to urinary levels. Urinary levels of N2O calculated from the regression line were the same as those obtained with the personal samplers. Environmental and urinary levels of N2O decreased significantly from the first to second test. In the second sampling 70% of subjects had levels of exposure to N2O and isoflurane within prescribed environmental limits (50 ppm for N2O and 0.5 ppm for isoflurane). At the first test anaesthetists had significantly higher levels of exposure to N2O than surgeons/instrument nurses. The survey demonstrated that: fixed position sampling data related to time spent in the operating theatre can be used to gauge individual exposure levels; exposure levels decrease after tests following implementation of preventive measures; monitoring needs to be repeated because exposure levels often exceed legal limits; occupational exposure decreases when pollution in the anaesthetic zone is reduced.

Risk of sporadic amyotrophic lateral sclerosis associated with seropositivity for herpesviruses and echovirus-7.

We examined the association between risk of sporadic amyotrophic lateral sclerosis (ALS) and seroprevalence of antibodies to echovirus-7 (echo-7) and herpesviruses 6, 7, and 8 through a population-based case-control study. We enrolled in a northern Italy area 20 newly diagnosed ALS cases and 20 referents. Risk of ALS was higher in subjects seropositive for echo-7 when we used the immunofluorescent assay, while little increase was noted with the neutralization test. Considering the different characteristics of these two serological assays, these results suggest an association between disease risk and infection with enterovirus (EV) family members (not specifically echo-7). ALS risk was slightly associated with seropositivity of human herpesvirus-6 (odds ratio: 3.2; p = 0.102) and more strongly with human herpesvirus-8 seropositivity (odds ratio: 8.4; p = 0.064), though these point estimates were statistically unstable due to the limited number of observed cases. The findings of this study warrant further investigation in larger studies of the possible etiologic role of EV or herpesvirus infection in sporadic ALS.

[Environmental concentrations of nitrous oxide and isoflurane in the operating theatre]. / Concentrazioni ambientali di protossido di azoto e isofluorano in sala operatoria.

An environmental survey was carried out in the operating theatres of an Emilian hospital (North Italy) to ascertain: if concentrations of nitrous oxide (N2O) and isoflurane were within prescribed limits; if anesthetic pollution decreases when it is periodically controlled; if the degree of pollution from isoflurane can be predicted from N2O measurements. Three controls of anesthetic pollution were carried out at six month intervals using a photoacoustic spectrometry analyser. Mean concentrations of N2O were lower than the limits prescribed for renovated (50 ppm) or not refurbished (100 ppm) operating theatres in 58% of the surgical sessions examined. Mean concentrations of isoflurane were lower than the values proposed for halogenated anesthetics, used together with N2O (0.5 ppm) or alone (2 ppm) in 39% of the cases. Anesthetic pollution decreased only after the second control. Mean concentrations of isoflurane and N2O were correlated with a very good degree of association (r = 0.77). The survey highlights that pollution needs to be controlled in operating room because anesthetic levels often exceed the prescribed limits. Awareness of the problem is important to improve environmental conditions. N2O measurement is indicative of pollution from isoflurane but halogenated anesthetic must also be determined for a thorough evaluation of anesthetic pollution.

Risk of birth defects in a population exposed to environmental lead pollution.

To investigate the relation between environmental lead and risk of birth defects in humans, we examined the prevalence at birth of congenital anomalies in an industrial area of northern Italy heavily polluted with lead. Through a population-based registry of birth defects, we identified anomalies diagnosed during three consecutive periods characterized by decreasing environmental lead exposure, 1982-1986, 1987-1990 and 1991-1995. In the lead-polluted area, we observed an excess risk of cardiovascular defects which decreased from 2.59 [95% confidence interval (CI) 1.68-3.82] in the first period to 1.18 (95% CI 0.62-2.06) and 0.97 (95% CI 0.57-1.54) in the subsequent periods. We also found an excess risk of oral clefts and musculoskeletal anomalies, with decreasing trends over time. We could not identify homogeneous patterns of temporal variation for other congenital anomalies, neither did we detect cases of neural tube defects. These results appear to support an association between severe parental lead exposure and specific birth defects.

Adverse health effects of selenium in humans.

Epidemiologic studies and case reports have shown that chronic exposure to selenium compounds is associated with several adverse health effects in humans. An early toxic effect of selenium is on endocrine function, particularly on the synthesis of thyroid hormones following dietary exposure of around 300 micrograms Se/d, and on the metabolism of growth hormone and insulin-like growth factor-1. Other adverse effects of selenium exposure can be the impairment of natural killer cells activity and at higher levels, hepatotoxicity and gastrointestinal disturbances. Dermatologic effects, such as nail and hair loss and dermatitis, occur after exposure to high levels of environmental selenium. Assessing the toxicity and morbidity after long-term exposure to environmental selenium is difficult: neurotoxicity, particularly the degeneration of motor neurons leading to increased risk of amyotrophic lateral sclerosis, might occur after chronic exposure to both organic and inorganic selenium compounds. The results of laboratory investigations and cohort studies suggest that selenium species exhibit a bivalent effect in cancer, either increasing or decreasing risk. Current environmental selenium exposure limits appear to be inadequate for averting adverse health effects.

The epidemiology of selenium and human cancer.

The relation between the trace element selenium and the etiology of cancer in humans remains elusive and intriguing, despite the number of epidemiologic studies published on the topic. We address some methodologic issues, such as misclassification of exposure, particularly to single selenium compounds, effect modification, confounding, and other sources of bias, which may explain the inconsistencies in the literature. We also review the results of cohort studies, which have yielded either inverse or null or direct associations between selenium exposure and subsequent cancer risk. To date, no beneficial effect on cancer incidence at major sites, including prostate cancer, has emerged from the Finnish program begun in 1984 to increase the average selenium intake in its population. Populations exposed to unusually high or low levels of environmental selenium might offer unique opportunities to investigate if selenium exposure is related to the etiology of human cancer.

Emotional stability, anxiety, and natural killer activity under examination stress.

This study was performed to evaluate the relation between a stable personality trait, a mood state and immune response to an examination stress. A self-reported measure of emotional stability (BFQ-ES scale) was obtained in a sample (n = 39) randomly selected from 277 cadets; this personality trait was also investigated by completing a neuroticism scale (Eysenck personality inventory) and a trait-anxiety scale (STAI). Natural killer (NK) cell activity was measured at baseline, long before the examination time and the examination day. The state-anxiety scale evaluated the response to the stressful stimulus. Taking subjects all together, the academic task did not result in significant modification over baseline in NK cell activity. Subjects were then divided into three groups based on emotional stability and state-anxiety scores: high emotional stability/low anxiety, medium, and low emotional stability/high anxiety. Examination stress induced significant increases in NK cell activity in the high emotional stability/low anxiety group, no effect in the medium group, and significant decreases in the low emotional stability/high anxiety group. The repeated-measure ANOVA revealed a significant interaction of group x period (baseline vs. examination) for both lytic units and percent cytolysis. The results did not change after introducing coffee and smoking habits as covariates. Our findings suggest that the state-anxiety acts in concert with a stable personality trait to modulate NK response in healthy subjects exposed to a psychological naturalistic stress. The relation between anxiety and poor immune control has been already described, whereas the ability of emotional stability to associate with an immunoenhancement has not yet reported. The peculiarity of our population, a very homogeneous and healthy group for life style and habits, can have highlighted the role of emotional stability, and may account for the difference with other studies.

Rising melanoma incidence in an Italian community from 1986 to 1997.

We examined the incidence of primary invasive melanoma in the municipality of Reggio Emilia, northern Italy, in the period from 1986 to 1997. We identified 169 cases, five of which were intraocular. After adjustment for confounders, the risk of having a thick melanoma (Breslow > or = 1 mm) did not decrease over time, except in older females. The age-standardized incidence of cutaneous melanoma during the entire study period was 7.57 in males and 11 in females; from 1986-1991 to 1992-1997, it rose from 5.04 to 10.04 cases/100,000 person-years in males and from 8.96 to 13.09 cases/100,000 person-years in females. In males, the increase in incidence was almost entirely confined to subjects aged 30 or more, suggesting a possible cohort effect. We noted rising age-standardized incidences over time both in males with thin tumours (Breslow < 1 mm) (from 2.05 to 4.38 cases/100,000 person-years) and thick tumours (from 2.73 to 5.51 cases/100,000 person-years), while in females the increase was limited to thin melanomas (from 3.14 to 6.93 cases/100,000 person-years), mainly due to an increase in the older age groups (50 69 years and > or =70 years). The increase in thick melanomas among males and the expected cohort effects suggests antecedent exposure to environmental risk factors.

Genetic polymorphisms influence variability in benzene metabolism in humans.

The role of genetic polymorphism in modulating urinary excretion of two benzene metabolites, i.e. trans,trans-muconic acid (t,t-MA) and S-phenylmercapturic acid (PMA), has been investigated in 59 non-smoking city bus drivers, professionally exposed to benzene via vehicle exhausts. Exposure to benzene was determined by personal passive samplers (mean +/- SD = 82.2 +/- 25.6 micrograms/m3), while internal dose and metabolic rate were evaluated by measuring urinary excretion of unmodified benzene (mean +/- SD = 361 +/- 246 ng/l), t,t-MA (mean +/- SD = 602 +/- 625 micrograms/g creatinine), and PMA (mean +/- SD = 5.88 +/- 4.76 micrograms/g creatinine). Genetic polymorphism at six loci encoding cytochrome-P450-dependent monooxygenases (CYP2E1 and CYP2D6), glutathione-S-transferases (GSTT1, GSTP1 and GSTM1) and NAD(P)H:quinone oxidoreductase (NQOR) was determined by polymerase chain reaction-based methods. No evidence emerged for a possible role of CYP2E1, GSTM1 and GSTP1 polymorphisms in determining the wide differences observed in the rate of benzene biotransformation. Conversely, a significantly higher t,t-MA urinary excretion was found to be correlated to, GSTT1 null genotype, and a significantly lower PMA excretion was detected in the subjects lacking NQOR activity and in the CYP2D6 extensive-metabolizers. Many biological (i.e. age and body burden) or lifestyle factors (i.e. rural or urban residence, use of paints and solvents, medication, alcohol and coffee intake), also taken into account as potential confounders, did not influence the correlations found. These findings suggest that CYP2D6, GSTT1 and NQOR polymorphisms contribute in explaining the metabolic variability observed in our sample. Therefore, these polymorphisms should be regarded as potential risk factors for benzene-induced adverse health effects.

Excess melanoma incidence in a cohort exposed to high levels of environmental selenium.

Epidemiological studies on the relation between selenium and human cancer have yielded strongly conflicting results. Prompted by the observation of a positive association between selenium intake and site-specific cancers, including melanoma, in a large cohort of nurses, we studied the 11-year melanoma incidence in an Italian cohort that consumed unusually high levels of inorganic selenium in tap water from 1975 to 1985. The setting was Reggio Emilia, an Italian municipality that provided a natural experiment relating to intake of high levels of inorganic selenium. We identified 2,065 individuals with high selenium exposure, who contributed a total of 20,179 person-years of follow-up, and we compared their experience with the 1,384,386 person-years of follow-up in the remaining population of Reggio Emilia. We included all cases of pathologically confirmed malignant melanoma, including intraocular melanoma, identified from the Reggio Emilia Hospital, the Bologna regional registry of hospital discharges, and the Milan National Cancer Institute. Eight cases of malignant melanoma occurred in the exposed cohort during the follow-up. Melanoma incidence was 3.9 times greater in the exposed than in the unexposed cohort (95% exact confidence limits, 1.8-7.4).

[Evaluation of the risk of neuropsychological damage from lead exposure in childhood]. / Valutazione del rischio di danno neuropsicologico per esposizione al piombo nell'infanzia.

Potential neurotoxicity of lead in children has been explored in many recent epidemiological studies carried out all over the world. Within a multicentric European study, an investigation was carried out also in Italy on children living in an industrial area and characterised by a non steady-state exposure condition with higher exposure at the early stages of life. This peculiar feature allowed to observe interesting associations between neurobehavioural functions and the levels of Pb measured in teeth, but not in blood. Indeed, Pb in teeth was associated with the results of psychometric tests which evaluate the discriminant ability and the attention. Other associations, like those found between the intelligence quotient (IQ) scores and Pb in teeth disappeared after correction for the socioeconomical status of parents. In general, in children exposed to environmental Pb, more consistent associations were found with visual-motor integration and attention than with IQ measurements. In agreement with literature data from other countries, we suggest that the relevance of neurotoxic effects of Pb is limited, at least at the current exposure levels, but also that a threshold Pb level associated with no effect cannot be identified.

Inter-individual variability of benzene metabolism to trans,trans-muconic acid and its implications in the biological monitoring of occupational exposure.

Unmodified benzene (UBz) and trans,trans-muconic acid (t,t-MA) were measured in urine samples collected at the end of the first half-shift in 80 bus drivers from a large city in Northern Italy. Mean UBz was 1155 ng/l (S.D. = 494), range 85-1980 ng/l; these values roughly correspond to 10-1000 micrograms/m3 of benzene in air. Mean t,t-MA was 297 micrograms/g creatinine; the range was large (20-1295 micrograms/g creatinine), and the distribution of values was bimodal. At further analysis of t,t-MA data, two subgroups of 59 and 18 subjects were identified (3 outliers were excluded): mean values of the index were 108 (S.D. = 65) and 916 (S.D. = 264) micrograms/g creatinine respectively, and the values within each subgroup were normally distributed. The mean ratio between t,t-MA and UBz in the subgroups were 0.15 and 0.85, respectively; the difference was significant. The first subgroup was defined as 'poor t,t-MA metabolizers', the other as 'efficient t,t-MA metabolizers'. No inter-subgroup differences were observed regarding the main characteristics (age, dietary and smoking habits, etc.). As the parent compound of t,t-MA, trans,trans-muconaldehyde is myelotoxic, and its production has been implicated in benzene-induced leukemia. 'efficient' t,t-MA metabolizers may be at higher risk of developing benzene toxicity. If confirmed in further studies, the inter-individual variability rate of metabolizing benzene to t,t-MA may introduce some limitations in the application of this metabolite as an exposure index of low benzene exposure. Nevertheless, the t,t-MA/UBz ratio may be an important index of susceptibility to benzene toxicity.

Zinc and copper status and blood pressure.

In order to elucidate the relationships between Zn and Cu and blood pressure, the present case-control study was carried out. Zn and Cu status was evaluated in 60 subjects, pharmacologically untreated, affected by mild stable hypertension and in 60 normotensives matched for sex, age and smoking habits. Different markers of Zn and Cu status, including serum, erythrocyte and urine levels of the two trace elements and activities of some Zn- or Cu-dependent enzymes (alkaline phosphatase, lactic dehydrogenase, superoxide dismutase and lysyl oxidase) were evaluated. No significant difference between hypertensives and normotensives was observed in the mean levels of Zn and Cu as well as in Zn- or Cu-dependent enzymes, though higher levels of serum copper were associated with increased risk of hypertension. Interesting relationships between the biological parameters investigated were observed in the hypertensive subjects. Inverse correlations between blood pressures and serum Zn were observed. Furthermore, blood pressure was inversely related to lysyl oxidase activity. These findings give further support to the hypothesis that an imbalance of Zn and Cu bioavailability may be associated to hypertensive condition.

Amyotrophic lateral sclerosis after long-term exposure to drinking water with high selenium content.

We examined 9 years' incidence of amyotrophic lateral sclerosis, a disease previously associated with a high-selenium environment, in a cohort of 5,182 residents of Reggio Emilia, Italy. This cohort had accidentally been exposed to drinking water with high selenium content. Four cases were diagnosed during the follow-up. Using the remainder of the municipal population as the reference group, the standardized incidence ratio was 4.22 (95% confidence interval = 1.15-10.80). The standardized incidence ratio was higher after limiting the analysis to the subcohort with the longest ascertainable exposure period. The findings appear to confirm a causal association between overexposure to environmental selenium and amyotrophic lateral sclerosis.

Epidemiological survey of amyotrophic lateral sclerosis in the province of Reggio Emilia, Italy: influence of environmental exposure to lead.

We carried out a retrospective incidence, prevalence and mortality survey of amyotrophic lateral sclerosis (ALS) in the province of Reggio Emilia, northern Italy. Based on 79 patients, the mean incidence per year for the period 1980 through 1992 was 1.5 cases per 100,000. On December 31st, 1992, the prevalence rate was 5.4 per 100,000. In the 10-year period of 1983-1992 the average mortality rate was 1.3 per 100,000 per year. The average age at onset was 61.3 +/- 10.2, the average survival period thereafter was 26.3 months +/- 17.7; 27.3 +/- 17.6 for classic ALS, 19.5 +/- 8.4 for progressive bulbar palsy and 36.3 +/- 41.4 for pseudopolyneuritic ALS. The incidence rate, recorded in public health district No.12, an area with documented lead pollution since the 1970s, was standardized to the sex and age of the population of the province. Its incidence and prevalence rate were comparable to the rates found in the remaining area of the province.

Serum selenium concentrations in patients with newly diagnosed lymphoid malignancies.

BACKGROUND: Increased mortality from lymphoid malignancies following exposure to environmental selenium has recently been reported. Moreover, conflicting results have been found in investigations examining the relationship between serum concentrations of selenium and some clinical features of malignant lymphoproliferative diseases. METHODS: Serum concentrations of selenium were analyzed by atomic absorption spectrometry in fifty-nine patients with newly diagnosed chronic lymphoid malignancies and in forty control subjects. RESULTS: Selenium concentrations were significantly lower in patients than in control subjects. However, when only patients with localized disease were compared to controls, no significant difference in serum selenium concentrations was observed. Clinical stage was inversely associated with selenium levels. High-grade non-Hodgkin's lymphoma was characterized by lower selenium levels than low-grade and intermediate-grade disease. Selenium levels were positively associated with albumin and hemoglobin, and inversely correlated with serum concentrations of beta 2-microglobulin and with erythrocyte sedimentation rate. CONCLUSIONS: The findings of this study do not suggest that a high selenium intake represents a risk factor for malignant lymphoproliferative diseases, but limitations of the investigation hamper evaluation of the results. The possible utility of determining serum concentrations of selenium in the clinical evaluation of patients with lymphoid malignancies merits examination in larger studies.

Cancer mortality in a residential cohort exposed to environmental selenium through drinking water.

Cancer mortality from 1986 to 1992 was examined in a cohort of 4419 individuals who had been residing in an area of the municipality of Reggio Emilia, northern Italy, where tap water with unusually high selenium content was accidentally supplied. Mortality for all cancers was not significantly different, both in males and in females, from that expected using death rates in the remaining municipal population as standard rates. No significant difference in mortality for site-specific cancers was observed in males, while in females a higher mortality for malignancies of the lymphatic-hematopoietic tissue overall considered and for non-Hodgkin's lymphoma was detected. Even if evaluation of the results is hampered by the low number of cancer deaths on which the analysis is based, findings of the study do not support the hypothesis of a strong inverse independent relationship between dietary intake of selenium and cancer mortality in humans.

Zinc, copper, and zinc- or copper-dependent enzymes in human hypertension.

Imbalance of zinc and copper status has been hypothesized in human hypertension. A case-control study was carried out to elucidate the possible relationship between zinc and copper status and essential hypertension. Thirty-one subjects affected by mild stable hypertension, pharmacologically untreated, were investigated together with 31 normotensive controls individually matched for sex, age, and smoking habits. Zinc and copper in serum and urine wee measured, and serum activities of alkaline phosphatase (AP), lactic dehydrogenase (LDH), copper-zinc superoxide dismutase (Cu-Zn SOD), lysyl oxidase (LOX), and monoamine oxidase (MAO) were evaluated. No significant difference in serum and urine zinc and copper content as far as in serum activity of zinc (AP and LDH) or copper (Cu-Zn SOD, LOX, and MAO)-dependent enzymes was found between hypertensives and normotensives. Positive relationships were found in normotensives between serum and urine levels of zinc (r = 0.577; p = 0.001) and copper (r = 0.394; p = 0.028), and between serum copper and Cu-Zn SOD (r = 0.534; p = 0.002). In normotensives, diastolic blood pressure and serum zinc were positively related (r = 0.370; p = 0.041). In hypertensives, inverse correlations were observed between diastolic blood pressure and AP (r = -0.498; p = 0.004) and Cu-Zn SOD (r = 0.452; p = 0.011), and between systolic blood pressure and LOX (r = -0.385; p = 0.033). Diastolic blood pressure was related to LDH inversely in hypertensives (r = -0.357; p = 0.049) and positively in normotensives (r = 0.457; p = 0.010). In normotensives, diastolic blood pressure was inversely related with MAO (r = -0.360; p = 0.046). These findings support the hypothesis that an imbalance of zinc and copper status might be involved in human hypertension.

Changes in drinking water selenium and mortality for coronary disease in a residential cohort.

In a part of the municipal territory of Reggio Emilia, northern Italy, selenium in drinking water decreased from 7 micrograms/L to less than 1 micrograms/L. In a cohort of 4419 individuals, previously exposed for at least 5 yr to the drinking water with higher selenium content, the 7-yr temporal distribution of deaths for coronary disease and for stroke was analyzed to examine a possible relationship with changes in drinking water selenium. From January 1986 until August 1988, when tap water selenium was 7 micrograms/L, deaths for coronary disease were one in males and two in females. After the decrease in drinking water selenium, 21 and 10 coronary deaths were observed, respectively, in males and in females from September 1988 to December 1992. No significant difference in the temporal distribution of stroke deaths was observed both in males and in females. Even if an effect of chance and aging in the temporal distribution of coronary deaths may not be excluded, findings of the study seem to be consistent with the hypothesis of a beneficial effect of selenium on coronary disease mortality.